Sulfadoxine-Pyrimethamine IPTp in Malawi: Effects on the gut and vaginal microbiomes Abstract Adverse birth outcomes, such as low birth weight, are common in sub-Saharan Africa. Much of it can be attributed to malaria. For nearly 20 years, pregnant women have been given therapeutic doses of sulfadoxine-pyrimethamine (SP) as intermittent preventive therapy (IPTp) to protect against malaria. SP-resistant malaria has become widespread; yet, paradoxically, IPTp with SP remains protective against adverse birth outcomes. SP is an antifolate with broad-spectrum antibacterial activity. We hypothesize that the protective effect of SP could be due to an effect on the gut or vaginal microbiome. As a first step toward testing this hypothesis, we will conduct an ancillary study on 50 pregnant women who are subjects in a large randomized control trial supported by the President?s Malaria Initiative in Malawi comparing SP and dihydroartemisinin-piperaquine as IPTp agents. Fecal samples and vaginal swabs will be obtained and sent to UNC where the 16S ribosomal RNA gene will be deep-sequenced by MiSeq and analyzed by QIIME. The effects of treatment on ?- and ?-diversity will be examined. We expect to find that SP causes decreased species richness and that individual microbiome profiles cluster according to treatment group. Currently the continued use of SP for IPTp is being debated in light of increasing SP resistance. If the beneficial effect of SP on birth outcome is mediated by its antibacterial effects, our findings would support the argument for continued IPTp-SP deployment.